tbuckley/cabot-search huggingface dataset:
Blockade of dual immune checkpoint inhibitory signals with a CD47/PD-L1 bispecific antibody for cancer treatment
Authors: Rongjuan Wang, Chang Zhang, Yuting Cao, Junchao Wang, Shasha Jiao, Jiao Zhang, Min Wang, Peipei Tang, Zijun Ouyang, Wenlu Liang, Yu Mao, An Wang, Gang Li, Jinchao Zhang, Mingzhu Wang, Shuang Wang, Xun Gui
Journal: Theranostics (2022)

Background: Even though PD-1/PD-L1 is an identified key "don't find me" signal to active adaptive immune system for cancer treatment, the overall response rate (ORR) for all cancer patients is still limited.Other effective therapeutic modalities to bridge the innate and adaptive immunity to improve ORR are urgently needed.Recently, CD47/SIRPα interaction is confirmed as a critical "don't eat me" signal to active innate immunity.However, the red blood cell (RBC) toxicity is the big concern for the development of CD47-based anti-cancer therapeutics.Methods: Here, we report the development of a CD47/PD-L1 bispecific antibody 6MW3211 to block both PD-1/PD-L1 and CD47/SIRPα signals, and studied the effects of 6MW3211 on anti-tumor immune functions in vitro and in vivo.The pharmacokinetic and toxicity profiles of 6MW3211 were evaluated in GLP non-human primate (NHP) studies. Results:The dual immune checkpoint inhibitory signaling blocker 6MW3211 shows high binding affinity to PD-L1 and low binding affinity to CD47.This inequivalent binding affinity design makes 6MW3211 preferentially bound to PD-L1 on tumor cells followed by disrupting the interaction of CD47/SIRPα.Complex structure determination and flow cytometry assay demonstrated that 6MW3211 has no binding to either human or rhesus monkey RBCs.6MW3211 effectively blocked both PD-1/DP-L1 and CD47/SIRPα signaling and promoted macrophage phagocytosis of tumor cells.Potent therapeutic efficacies of 6MW3211 in three different mouse models were further observed.Moreover, 6MW3211 was demonstrated to have a fairly good safety profile in a GLP NHP study.In addition, multiplex fluorescent immunohistochemistry (mIHC) staining shows that PD-L1 and CD47 co-express on several different types of human tumor tissues.Conclusions: These results support the development of 6MW3211 for the treatment of PD-L1 and CD47 double positive cancers.
Stiff matrix induced srGAP2 tension gradients control migration direction in triple-negative breast cancer
Authors: Chen Li, Zihui Zheng, Xiang Wu, Qiu Xie, Ping Liu, Yunfeng Hu, Mei Chen, Liming Liu, Wangxing Zhao, Linlin Chen, Jun Guo, Ying Song
Journal: Theranostics (2022)

Rationale: Cells migrating through interstitial matrix enables stiffening of the tumor micro-environment. To overcome the stiff resistance of extracellular matrix, aggressive cells require the extracellular mechanosensory activation and intracellular tension response. Mechanotransduction linker srGAP2 can synergistically control the mechanical-biochemical process of malignant cell migration. Methods: To mimic the tumor micro-environment containing abundant collagen fibers and moving durotaxis of triple-negative breast cancer cells, the stiff-directed matrix was established. The newly designed srGAP2 tension probe was used to real-time supervise srGAP2 tension in living cells. The phosphorylation sites responsible for srGAP2 tension were identified by phosphorylated mutagenesis. Transwell assays and Xenograft mouse model were performed to evaluate TNBC cells invasiveness in vitro and in vivo. Fluorescence staining and membrane protein isolation were used to detect protein localization. Results: The present study shows srGAP2 serves as a linker to transmit the mechanical signals among cytoskeleton and membrane. SrGAP2 exhibits tension gradients among different parts in the stiff-directionally migrating triple-negative breast cancer cells. Cells showing the polarized tension that increased in the leading edge move faster, particularly guided by the stiff interstitial matrix. The srGAP2 tension-directed cell migration results from the upstream events of PKCα-mediated phosphorylation at Ser206 in the F-bar domain of srGAP2. In addition, Syndecan-4 (SDC4), a transmembrane mechanoreceptor protein, drives PKCα regional recruit on the area of membrane trending deformation, which requires the distinct extent of extracellular mechanics. Conclusion: SDC4-PKCα polarized distribution leads to the intracellular tension gradient of srGAP2, presenting the extra- and intracellular physiochemical integration and essential for persistent cell migration in stiff matrix and caner progression. Targeting the srGAP2-related physicochemical signaling could be developed into the therapeutic strategies of inhibiting breast cancer cell invasion and durotaxis.
Recent advances in the medical applications of hemostatic materials
Authors: Yu Guo, Min Wang, Qi Liu, Guoliang Liu, Shuang Wang, Jiannan Li
Journal: Theranostics (2022)

Bleeding caused by trauma or surgery is a serious health problem, and uncontrollable bleeding can result in death.Therefore, developing safe, effective, and convenient hemostatic materials is important.Active hemostatic agents currently used to investigate the field of hemostasis are divided into four broad categories: natural polymers, synthetic polymers, inorganic materials, and metal-containing materials.Hemostatic materials are prepared in various forms for wound care applications based on the active ingredients used.These materials include nanofibers, gels, sponges, and nanoparticles.Hemostatic materials find their applications in the field of wound care, and they are also used for hemostasis during malignant tumor surgery.Prompt and effective hemostasis can reduce the possibility of the spread of tumor cells with blood.This review discusses the outcomes of current research conducted in the field and the problems persisting in the field of developing hemostatic materials.The review also presents a platform for the further development of hemostatic materials.Bleeding caused by trauma or surgery is a serious health problem, and uncontrollable bleeding can result in death.Therefore, developing safe, effective, and convenient hemostatic materials is important.Active hemostatic agents currently used to investigate the field of hemostasis are divided into four broad categories: natural polymers, synthetic polymers, inorganic materials, and metal-containing materials.Hemostatic materials are prepared in various forms for wound care applications based on the active ingredients used.These materials include nanofibers, gels, sponges, and nanoparticles.Hemostatic materials find their applications in the field of wound care, and they are also used for hemostasis during malignant tumor surgery.Prompt and effective hemostasis can reduce the possibility of the spread of tumor cells with blood.This review discusses the outcomes of current research conducted in the field and the problems persisting in the field of developing hemostatic materials.The review also presents a platform for the further development of hemostatic materials.
Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy
Authors: Yuan-Hua Wu, Rong-Jane Chen, Hui-Wen Chiu, Li-Xing Yang, Yung-Li Wang, Yu-Ying Chen, Ya-Ling Yeh, Mei-Yi Liao, Ying-Jan Wang
Journal: Theranostics (2022)

Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.
Role of primary aging hallmarks in Alzheimer´s disease
Authors: Jin Zhao, Jisen Huai
Journal: Theranostics (2022)

Alzheimer's disease (AD) is the most common neurodegenerative disease, which severely threatens the health of the elderly and causes significant economic and social burdens.The causes of AD are complex and include heritable but mostly aging-related factors.The primary aging hallmarks include genomic instability, telomere wear, epigenetic changes, and loss of protein stability, which play a dominant role in the aging process.Although AD is closely associated with the aging process, the underlying mechanisms involved in AD pathogenesis have not been well characterized.This review summarizes the available literature about primary aging hallmarks and their roles in AD pathogenesis.By analyzing published literature, we attempted to uncover the possible mechanisms of aberrant epigenetic markers with related enzymes, transcription factors, and loss of proteostasis in AD.In particular, the importance of oxidative stress-induced DNA methylation and DNA methylation-directed histone modifications and proteostasis are highlighted.A molecular network of gene regulatory elements that undergoes a dynamic change with age may underlie age-dependent AD pathogenesis, and can be used as a new drug target to treat AD.
A new organic molecular probe as a powerful tool for fluorescence imaging and biological study of lipid droplets
Authors: Ri Zhou, Chenguang Wang, Xishuang Liang, Fangmeng Liu, Peng Sun, Xu Yan, Xiaoteng Jia, Xiaomin Liu, Yue Wang, Geyu Lu
Journal: Theranostics (2022)

Background: Lipid droplets (LDs) are critical organelles associated with many physiological processes in eukaryotic cells.To visualize and study LDs, fluorescence imaging techniques including the confocal imaging as well as the emerging super-resolution imaging of stimulated emission depletion (STED), have been regarded as the most useful methods.However, directly limited by the availability of advanced LDs fluorescent probes, the performances of LDs fluorescence imaging are increasingly unsatisfied with respect to the fast research progress of LDs.Methods: We herein newly developed a superior LDs fluorescent probe named Lipi-QA as a powerful tool for LDs fluorescence imaging and biological study.Colocalization imaging of Lipi-QA and LDs fluorescent probe Ph-Red was conducted in four cell lines.The LDs staining selectivity and the photostability of Lipi-QA were also evaluated by comparing with the commercial LDs probe Nile Red.The in-situ fluorescence lifetime of Lipi-QA in LDs was determined by time-gated detection.The cytotoxicity of Lipi-QA was assessed by MTT assay.The STED saturation intensity as well as the powerand gate time-dependent resolution were tested by Leica SP8 STED super-resolution nanoscopy.The time-lapse 3D confocal imaging and time-lapse STED super-resolution imaging were then designed to study the complex physiological functions of LDs.Results: Featuring with the advantages of the super-photostability, high LDs selectivity, long fluorescence lifetime and low STED saturation intensity, the fluorescent probe Lipi-QA was capable of the long-term time-lapse three-dimensional (3D) confocal imaging to in-situ monitor LDs in 3D space and the time-lapse STED super-resolution imaging (up to 500 STED frames) to track the dynamics of LDs with nanoscale resolution (37 nm).Conclusions: Based on the state-of-the-art fluorescence imaging results, some new biological insights into LDs have been successfully provided.For instance, the long-term time-lapse 3D confocal imaging has surely answered an important and controversial question that the number of LDs would significantly decrease rather than increase upon starvation stimulation; the time-lapse STED super-resolution imaging with the highest resolution has impressively uncovered the fission process of nanoscale LDs for the first time; the starvation-induced change of LDs in size and in speed has been further revealed at nanoscale by the STED super-resolution imaging.All of these results not only highlight the utility of the newly developed fluorescent probe but also significantly promote the biological study of LDs.
Borneol-driven meningeal lymphatic drainage clears amyloid-β peptide to attenuate Alzheimer-like phenotype in mice
Authors: Yue Wu, Tingting Zhang, Xianqiang Li, Yimei Wei, Xinyu Li, Sixue Wang, Jun Liu, Dan Li, Shujun Wang, Tiantian Ye
Journal: Theranostics (2022)

Rationale: The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aβ and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aβ from the brain. Methods: We investigated the effect of borneol on meningeal lymphatic clearance of macromolecules with different molecular weights (including Aβ) in the brain. To further investigate the mechanism of borneol regulating meningeal lymphatic drainage, immunofluorescence staining, western blotting, ELISA, RT-qPCR, and Nitric Oxide assay kits were used. The cognitive function of AD mice after borneol treatment was evaluated using two behavioral tests: open field (OF) and Morris water maze (MWM). Results: This study discovered that borneol could accelerate the lymphatic clearance of Aβ from the brain by enhancing meningeal lymphatic drainage. Preliminary mechanism analysis revealed that borneol could improve the permeability and inner diameter of lymphatic vessels, allowing macromolecules to drain into the cervical lymph nodes (CLNS) and then be transported to the lymphatic circulation. To speed up the clearance of macromolecules, borneol also stimulated lymphatic constriction by lowering the level of nitric oxide in the meninges. In addition, borneol stimulated lymphangiogenesis by increasing the levels of FOXC2, VEGFC, and LYVE-1 in the meninges, which promoted the clearance rates of macromolecules. Borneol improved meningeal lymphatic clearance not only for Aβ but also for other macromolecular polymers (molecular weight in the range of 2 KD - 45 KD. Borneol ameliorated cognitive deficits and alleviated brain Aβ burden in Aβ-injected mice. Conclusions: Our findings not only provide a strategy to regulate lymphatic clearance pathways of macromolecules in the brain, but also new targets and ideas for treating neurodegenerative diseases like AD. Furthermore, our findings indicate that borneol is a promising therapeutic drug for AD.
Epigallocatechin-3-gallate/mineralization precursors co-delivery hollow mesoporous nanosystem for synergistic manipulation of dentin exposure
Authors: Jian Yu, Haolin Bian, Yaning Zhao, Jingmei Guo, Chenmin Yao, He Liu, Ya Shen, Hongye Yang, Cui Huang
Journal: Bioactive Materials (2022)

As a global public health focus, oral health plays a vital role in facilitating overall health. Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases. The exposed dentinal tubules provide channels for irritants and bacterial invasion, leading to dentin hypersensitivity and even pulp inflammation. Cariogenic bacterial adhesion and biofilm formation on dentin are responsible for tooth demineralization and caries. It remains a clinical challenge to achieve the integration of tubule occlusion, collagen mineralization, and antibiofilm functions for managing exposed dentin. To address this issue, an epigallocatechin-3-gallate (EGCG) and poly(allylamine)-stabilized amorphous calcium phosphate (PAH-ACP) co-delivery hollow mesoporous silica (HMS) nanosystem (E/PA@HMS) was herein developed. The application of E/PA@HMS effectively occluded the dentinal tubules with acid- and abrasion-resistant stability and inhibited the biofilm formation of Streptococcus mutans. Intrafibrillar mineralization of collagen fibrils and remineralization of demineralized dentin were induced by E/PA@HMS. The odontogenic differentiation and mineralization of dental pulp cells with high biocompatibility were also promoted. Animal experiments showed that E/PA@HMS durably sealed the tubules and inhibited biofilm growth up to 14 days. Thus, the development of the E/PA@HMS nanosystem provides promising benefits for protecting exposed dentin through the coordinated manipulation of dentin caries and hypersensitivity.
A biomimetic piezoelectric scaffold with sustained Mg2+ release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration
Authors: Liangyu Wang, Yanyun Pang, Yujing Tang, Xinyu Wang, Daixing Zhang, Xu Zhang, Yingjie Yu, Xiaoping Yang, Qing Cai
Journal: Bioactive Materials (2022)

Natural bone is a composite tissue made of organic and inorganic components, showing piezoelectricity. Whitlockite (WH), which is a natural magnesium-containing calcium phosphate, has attracted great attention in bone formation recently due to its unique piezoelectric property after sintering treatment and sustained release of magnesium ion (Mg2+). Herein, a composite scaffold (denoted as PWH scaffold) composed of piezoelectric WH (PWH) and poly(ε-caprolactone) (PCL) was 3D printed to meet the physiological demands for the regeneration of neuro-vascularized bone tissue, namely, providing endogenous electric field at the defect site. The sustained release of Mg2+ from the PWH scaffold, displaying multiple biological activities, and thus exhibits a strong synergistic effect with the piezoelectricity on inhibiting osteoclast activation, promoting the neurogenic, angiogenic, and osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat calvarial defect model, this PWH scaffold is remarkably conducive to efficient neo-bone formation with rich neurogenic and angiogenic expressions. Overall, this study presents the first example of biomimetic piezoelectric scaffold with sustained Mg2+ release for promoting the regeneration of neuro-vascularized bone tissue in vivo, which offers new insights for regenerative medicine.
Comparison of Demographic, Clinical, Biochemical, and Imaging Findings in Hypertrophic Cardiomyopathy Prognosis
Authors: Georgios Georgiopoulos, Stefano Figliozzi, Konstantinos Pateras, Flavia Nicoli, Dimitrios Bampatsias, Matteo Beltrami, Gherardo Finocchiaro, Amedeo Chiribiri, Pier Giorgio Masci, Iacopo Olivotto
Journal: JACC Heart Failure (2022)
Acknowledging geodiversity in safeguarding biodiversity and human health
Authors: Janne Alahuhta, Helena Tukiainen, Maija Toivanen, Terhi Ala-Hulkko, Vahid Farrahi, Jan Hjort, Tiina M Ikäheimo, Tiina Lankila, Tuija Maliniemi, Soile Puhakka, Henriikka Salminen, Marjo Seppänen, Raija Korpelainen, Ding Ding
Journal: The Lancet Planetary Health (2022)

Our existence on Earth is founded on a vital nature, which supports human physical and mental health. However, nature is often depicted only through biodiversity, whereas geodiversity-the diversity of non-living nature-has so far been neglected. Geodiversity consists of assemblages, structures, and systems of geological, geomorphological, soil, and hydrological components that fundamentally underlie biodiversity. Biodiversity can support overall human health only with the foundation of geodiversity. Landscape characteristics, such as varying topography or bodies of water, promote aesthetic and sensory experiences and are also a product of geodiversity. In this Personal View, we introduce the concept of geodiversity as a driver for planetary health, describe its functions and services, and outline the intricate relationships between geodiversity, biodiversity, and human health. We also propose an agenda for acknowledging the importance of geodiversity in health-related research and decision making. Geodiversity is an emerging topic with untapped potential for ensuring ecosystem functionality and good living conditions for people in a time of changing environments.
Environmental sustainability in national food-based dietary guidelines: a global review
Authors: Genevieve James-Martin, Danielle L Baird, Gilly A Hendrie, Jessica Bogard, Kim Anastasiou, Paige G Brooker, Bonnie Wiggins, Gemma Williams, Mario Herrero, Mark Lawrence, Amanda J Lee, Malcolm D Riley
Journal: The Lancet Planetary Health (2022)
Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study
Authors: Goodluck Willey Lyatuu, Roseline Urrio, Helga Naburi, Peter Lyaruu, Brenda Simba, Hellen Siril, Emmanuel Philipo, Lameck Machumi, Ayoub Kibao, Deborah Kajoka, Mukome Nyamhagatta, David Sando, Gunnel Biberfeld, Nicola Orsini, Charles Kilewo, Anna Mia Ekström
Journal: The Lancet HIV (2022)
Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB
Authors: Ryuta Uraki, Mutsumi Ito, Yuri Furusawa, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Eisuke Adachi, Makoto Saito, Michiko Koga, Takeya Tsutsumi, Shinya Yamamoto, Amato Otani, Maki Kiso, Yuko Sakai-Tagawa, Hiroshi Ueki, Hiroshi Yotsuyanagi, Masaki Imai, Yoshihiro Kawaoka
Journal: The Lancet Infectious Diseases (2022)